English abstract

Mice with mutation in the Fas-ligand gene develop generalised lymphoproliferative disorder (gld mice), characterised by accumulation of double negative (DN) T cells (CD4–CD8–), as well as higher bone mineral density and more trabecular bone. To evaluate the role of immune system in the development of bone phenotype of gld mice, we parabiotically joined the wild-type (C57BL/6, B6) with gld mice. The mice were sacrificed weekly for four weeks. Additionally, the mice were separated after four weeks and sacrificed two weeks after separation. Lymphoproliferative disorder was suppressed in gld mice during the first week and the suppression was evident even after the animals were separated. The proportion of DN T cells in the lymphoid tissues of B6 increased during parabiosis, suggesting that the immune phenotype of B6 mice became similar to that of gld mice. At the same time, the bone phenotype of B6 animals shifted towards the gld bone phenotype. The number of osteoclast precursors in the cell culture of B6 bone marrow decreased at one and four weeks, while the number of osteoblast precursors increased at four weeks after parabiosis. The alterations of B6 bone marrow during parabiosis were paralleled by increased expression of cytokine osteoprotegerin in the bone, both at the gene and the protein levels, suggesting that osteoprotegerin was the link between the bone and immune phenotype. Simultaneous transfer of both immune and bone phenotype from gld to B6 mice point to the immune component of gld bone phenotype. On the other hand, lack of changes in the bone marrow of gld mice during parabiosis indicated that Fas-ligand has a direct role in the formation of bone phenotype of gld mice.